To purify and characterize the postulated inhibitor in SCID patients. Its potential for inhibiting lymphocyte differentiation will be tested and its effects on purine metabolism of fibroblasts from normal and immunodeficient patients will be examined. A detailed study of the ADase isozymes in tip and crypt cells of human small intestines and colon as well as from various human neoplastic tissues is planned. In conjunction with similar studies on the rat, these data should help in understanding whether colon tumors arise from crypt or tip cells, and therefore should aid in the design of anti-tumor agents. We shall attempt to establish the subunit structure of the several ADase isozymes. In particular hybridization of subunits will be utilized to determine subunit numerology. These data should clarify the nature of the regulation of tissue ADase activity by the reported protein conversion factor. The enzyme found in various human and animal tumors will be purified employing immunosorbents and the subunit structure compared to that of normal enzyme. BIBLIOGRAPHIC REFERENCES: Trotta, P.P., Smithwick, E.M., and Balis, M.E. (1976). A Normal Level of Adenosine Deaminase Activity in the Red Cell Lysates of Carriers and Patients with Severe Combined Immunodeficiency Disease, Proc. Nat'l. Acad. Sci. (U.S.A) 73: 104-108. Trotta, P.P., Smithwick, E.M., Good, R.A. and Balis, M.E. (1976). Characterization of Adenosine Deaminase from Red Cell Lysates of Carriers and Patients with Severe Combined Immunodeficiency, Amer. Soc. Bio. Chem. Abstracts, San Francisco, Calif.